This is a competitive renewal application for the Philadelphia Pediatric AIDS Clinical Trials Unit (PACTU), a consortium consisting of The Children's Hospital of Philadelphia (CHOP) as the main unit, St. Christopher's Hospital of Philadelphia as a pediatric subunit and four perinatal subunits, the Hospital of the University of Pennsylvania, Temple University Hospital, Thomas Jefferson University Hospital, and Hahnemann University Hospital. The Philadelphia PACTU has maintained a strong performance record over the past grant period, qualifying for incentive awards in each of the past two years. The Philadelphia PACTU also competed successfully to become one of the sites funded through the PACTG Adolescent Initiative. The Philadelphia PACTU has been highly effective in enrolling subjects into perinatal, primary therapy, adolescent, complications of therapy, and immunology/ immune-based therapy/vaccine protocols. In the past two years, an aggressive effort to promote participation in adolescent studies resulted in enrollment of three adolescents into PACTG 381. The Philadelphia PACTU has an outstanding record of administrative performance and compliance with regulatory and data management procedures. Several members of the Philadelphia PACTU hold leadership positions in the PACTG and are making major contributions to the scientific agenda. During the next grant period, the Philadelphia PACTU will: 1) enroll an increased number of adolescents into protocols; 2) maintain its excellent record of compliance with regulatory and data management procedures; and 3) contribute in a major way to the scientific agenda of the PACTG. In particular, members of the Philadelphia PACTU will direct the following studies: virologic and immunologic effects of long-term effective combination therapy (PACTG 382), safety and immunologic effects of interleukin-2 (PACTG 299), immune reconstitution in adolescents receiving HAART (PACTG 381), novel antiretroviral combinations in infants, children and adolescents (PACTG 1020), and both preventive and therapeutic HIV vaccines.